Prevalence of mitochondrial DNA disease in adults

Abstract

ObjectiveDiverse and variable clinical features, a loose genotype–phenotype relationship, and presentation to different medical specialties have all hindered attempts to gauge the epidemiological impact of mitochondrial DNA (mtDNA) disease. Nevertheless, a clear understanding of its prevalence remains an important goal, particularly about planning appropriate clinical services. Consequently, the aim of this study was to accurately define the prevalence of mtDNA disease (primary mutation occurs in mtDNA) in the working‐age population of the North East of England.MethodsAdults with suspected mitochondrial disease in the North East of England were referred to a single neurology center for investigation from 1990 to 2004. Those with pathogenic mtDNA mutations were identified and pedigree analysis performed. For the midyear period of 2001, we calculated the minimum point prevalence of mtDNA disease for adults of working age (>16 and <60/65 years for female/male patients, respectively).ResultsIn this population, we found that 9.2 in 100,000 people have clinically manifest mtDNA disease, making this one of the commonest inherited neuromuscular disorders. In addition, a further 16.5 in 100,000 children and adults younger than retirement age are at risk for development of mtDNA disease.InterpretationThrough detailed pedigree analysis and active family tracing, we have been able to provide revised minimum prevalence figures for mtDNA disease. These estimates confirm that mtDNA disease is a common cause of chronic morbidity and is more prevalent than has been previously appreciated. Ann Neurol 2007

Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease

“…These current results for mtDNA mutations are similar to that reported previously in adult patients with mitochondrial disease in the North East of England a decade earlier and as such act as comparative data 3. Although the frequency of mtDNA mutations remain stable in our patient cohort, the point prevalence for the m.3243A>G mutation remains significantly lower than the frequency reported by Majamaa et al21 The reasons for this remain unclear.…”

“…The minimum point prevalence figure for all clinical disease due to mtDNA mutations in this study is comparable with our previously published point prevalence of ≈1 in 5,0003; reflecting the stability of mtDNA disease prevalence both geographically and over time. This also reflects the relative stability of the population of the North East, where ONS census data8 showed only a 2.2% increase in the regional population numbers compared to a 7% increase in national figures in the intervening decade.…”

“…Comprehensive pedigree analysis and family tracing was performed, identifying other clinically affected individuals and also unaffected family members at risk of disease. In contrast to our previous study,3 improvements in noninvasive testing4, 5 have allowed us to include elderly individuals, beyond working age, where a positive genetic diagnosis was confirmed.…”

Mutations in mitochondrially encoded complex I enzyme as the second common cause in a cohort of Chinese patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes

“…The A3243G mutation was also the most frequently encountered mtDNA mutation in a large series of patients with suspected mitochondrial disease. 16,21 The G13513A mutation in the MTND5 was the second-most common mutation of MELAS (7.6%) following A3243G. If considering the mutations of ND3, ND4 and ND5 subunits together, MTND genes will be the second hotspot mutations, accounting for 12% of the mtDNA mutations causing MELAS in this test group.…”

How Can We Treat Mitochondrial Encephalomyopathies? Approaches to Therapy

“…10 These figures suggest that mtDNA disease is a common cause of chronic morbidity and is more prevalent than previously thought. This not only has implications for allocation of health care resources, but also highlights the need to develop new approaches to the clinical management of patients 11 with mitochondrial disease.…”